Heap / Prosser / Lamming Biotechnology in Growth Regulation

1. Auflage 2013
ISBN: 978-1-4831-0083-8
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 296 Seiten

Biotechnology in Growth Regulation focuses on mechanisms of action of growth hormones and how immunological and transgenic procedures can affect growth response. The book first examines species specificity and structure-function relationship of growth hormones. Microheterogeneity of growth hormones; variations in amino acid sequence and biological properties of growth hormones; and structure-function relationship are discussed. The text also looks at growth hormone receptors and binding proteins; regulation of growth hormone receptors; modulations of growth hormone release; and neuroregulation of growth hormone secretion. The book then discusses the role of growth hormones in the regulation of adipocyte growth and function. Chronic effects of growth hormones on insulin action and lipid synthesis; effects of growth hormones on lipolysis; and adipogenesis are also described. The text looks at growth-promoting properties of recombinant growth hormones and mechanisms by which porcine growth hormone enhances growth in pigs. The book also highlights the direct effects of growth hormones on osteogenesis and chondrogenesis; action of IGF-I on mammary function; antigen-antibody complexes that enhance growth; and transgenics. The text also presents experiments that show the effects of growth hormones on animals. The book is a good source of information for readers wanting to study growth hormones.

Autoren/Hrsg.

Heap, R. B.

Prosser, C. G.

Lamming, G. E.

Inhaltsverzeichnis

1;Front Cover;1
2;Biotechnology in Growth Regulation;4
3;Copyright Page;5
4;PREFACE;6
5;LIST OF SPONSORS;7
6;Table of Content;8
7;Part 1. GROWTH HORMONE;12
7.1;Chapter 1. SPECIES SPECIFICITY AND STRUCTURE-FUNCTION RELATIONSHIPS OF GROWTH HORMONE;14
7.1.1;INTRODUCTION;14
7.1.2;MICROHETEROGENEITY OF GROWTH HORMONE;14
7.1.3;SPECIES SPECIFICITY OF GROWTH HORMONES: VARIATIONS IN AMINO ACID SEQUENCE;14
7.1.4;SPECIES SPECIFICITY OF GROWTH HORMONES: VARIATIONS IN BIOLOGICAL PROPERTIES;18
7.1.5;STRUCTURE-FUNCTION RELATIONSHIPS;18
7.1.6;CONCLUSIONS;21
7.1.7;REFERENCES;21
7.2;Chapter 2. GROWTH HORMONE RECEPTORS AND BINDING PROTEINS;26
7.2.1;INTRODUCTION;26
7.2.2;RECEPTOR PURIFICATION AND CLONING;27
7.2.3;SERUM BINDING PROTEIN;29
7.2.4;HOMOLOGY WITH THE PROLACTIN RECEPTOR;31
7.2.5;PROSPECTIVE;32
7.2.6;ACKNOWLEDGEMENTS;32
7.2.7;REFERENCES;33
7.3;Chapter 3. THE REGULATION OF THE GROWTH HORMONE RECEPTOR;38
7.3.1;INTRODUCTION;38
7.3.2;HETEROGENEITY OF THE GH RECEPTOR;38
7.3.3;ONTOGENY OF GH RECEPTORS;39
7.3.4;ENDOCRINE AND METABOLIC REGULATION OF THE GH RECEPTOR;40
7.3.5;CONCLUDING REMARKS;42
7.3.6;ACKNOWLEDGEMENTS;42
7.3.7;REFERENCES;42
7.4;Chapter 4. MODULATION OF GROWTH HORMONE RELEASE: FROM CNS TO THE SECRETORY EVENT;46
7.4.1;INTRODUCTION;46
7.4.2;GHRH AND SS IN THE HYPOTHALAMUS;46
7.4.3;OTHER HYPOTHALAMIC FACTORS INFLUENCING GH RELEASE;46
7.4.4;CONTROL OF HYPOTHALAMIC PEPTIDES;47
7.4.5;EPISODIC GH RELEASE;49
7.4.6;SOMATOTROPHS, SECOND MESSENGERS AND ION CHANNELS;50
7.4.7;GHRH CONTROL OF GH RELEASE;50
7.4.8;SS CONTROL OF GH RELEASE;52
7.4.9;INTERRELATIONSHIPS BETWEEN GH SECRETING FACTORS;52
7.4.10;CODA;53
7.4.11;ACKNOWLEDGEMENTS;53
7.4.12;REFERENCES;53
7.5;Chapter 5. NEUROREGULATION OF GROWTH HORMONE SECRETION;58
7.5.1;INTRODUCTION;58
7.5.2;PEPTIDERGIC CONTROL OF GH RELEASE;59
7.5.3;FEEDBACK PATHWAYS AND CHOLINERGIC CONTROL;61
7.5.4;REFERENCES;64
7.6;Chapter 6. ROLE OF GROWTH HORMONE IN THE REGULATION OF ADIPOCYTEGROWTH AND FUNCTION;68
7.6.1;INTRODUCTION;68
7.6.2;RECEPTORS FOR GH AND IGFs;68
7.6.3;CHRONIC EFFECTS OF GH ON INSULIN ACTION AND LIPID SYNTHESIS;69
7.6.4;ACUTE, INSULIN-LIKE EFFECTS OF GH ON ADIPOCYTE METABOLISM;71
7.6.5;EFFECTS OF GH ON LIPOLYSIS;72
7.6.6;MEDIATION BY IGFs;73
7.6.7;ADIPOGENESIS;74
7.6.8;CONCLUSIONS;75
7.6.9;REFERENCES;75
7.7;Chapter 7. A COMPARISON OF THE MECHANISMS OF ACTION OF BOVINE PITUITARY-DERIVED AND RECOMBINANT SOMATOTROPIN (ST)IN INDUCING GALACTOPOIESIS IN THE COW DURING LATELACTATION;84
7.7.1;INTRODUCTION;84
7.7.2;EXPERIMENTAL;84
7.7.3;RESULTS AND DISCUSSION;86
7.7.4;COMMENT;88
7.7.5;ACKNOWLEDGEMENTS;92
7.7.6;REFERENCES;93
7.8;Chapter 8. GROWTH PROMOTING PROPERTIES OF RECOMBINANT GROWTH HORMONE;96
7.8.1;INTRODUCTION;96
7.8.2;THE PHYSIOLOGICAL ROLE OF ENDOGENOUS GH;96
7.8.3;EXOGENOUS GH: GROWTH AND BODY COMPOSITION;96
7.8.4;THE INTERACTION BETWEEN GH AND OTHER ANABOLIC HORMONES;98
7.8.5;THE EFFECTS OF GH ON METABOLISM BY SPECIFIC TISSUES;99
7.8.6;VARIABILITY OF RESPONSIVENESS TO EXOGENOUS GH;103
7.8.7;CONCLUSIONS: THE FUTURE;104
7.8.8;ACKNOWLEDGEMENTS;105
7.8.9;REFERENCES;105
7.9;Chapter 9. THE MECHANISMS BY WHICH PORCINE GROWTH HORMONE IMPROVES PIG GROWTH PERFORMANCE;108
7.9.1;INTRODUCTION;108
7.9.2;METABOLIC EFFECTS OF pGH;110
7.9.3;SOMATOGENIC EFFECTS OF pGH;112
7.9.4;SUMMARY;113
7.9.5;REFERENCES;114
7.10;Chapter 10. EVALUATION OF SOMETRIBOVE (METHIONYL BOVINE SOMATOTROPIN) IN TOXICOLOGY AND CLINICAL TRIALS IN EUROPE AND THEUNITED STATES;118
7.10.1;INTRODUCTION;118
7.10.2;TOXICOLOGY EXPERIMENTS;118
7.10.3;CLINICAL TESTING;121
7.10.4;FARM TRIALS;123
7.10.5;SOMETRIBOVE AND THE DETECTION OF TREATED COWS;126
7.10.6;CONCLUSION;126
7.10.7;REFERENCES;126
8;Part 2.
GROWTH FACTORS;128
8.1;Chapter 11. GROWTH PROMOTION USING RECOMBINANT INSULIN-LIKE GROWTH FACTOR-I;130
8.1.1;INTRODUCTION;130
8.1.2;HYPOPHYSECTOMIZED RATS;130
8.1.3;YOUNG MINI-POODLES;132
8.1.4;SUMMARY AND CONCLUSIONS;132
8.1.5;REFERENCES;133
8.2;Chapter 12. THE DIRECT EFFECTS OF GROWTH HORMONE ON CHONDROGENESIS AND OSTEOGENESIS;134
8.2.1;INTRODUCTION;134
8.2.2;MECHANISTIC THEORIES OF GH ACTION;134
8.2.3;GH EFFECTS ON ORGAN CULTURE OF MANDIBULAR CONDYLES;135
8.2.4;GH EFFECTS IN TISSUE CULTURE OF CHONDROPROGENITOR CELLS;135
8.2.5;GH EFFECTS ON THE OSSIFICATION FRONT;135
8.2.6;GH EFFECTS ON THE BONE MARROW;136
8.2.7;CONCLUSIONS;136
8.2.8;ACKNOWLEDGEMENTS;136
8.2.9;REFERENCES;136
8.3;Chapter 13. GROWTH PROMOTION BY GROWTH HORMONE AND INSULIN-LIKE GROWTH FACTOR-I IN THE RAT;140
8.3.1;INTRODUCTION;140
8.3.2;THE HYPOPHYSECTOMIZED RAT;140
8.3.3;NORMAL RATS;141
8.3.4;IN VIVO GROWTH-PROMOTING EFFECTS OF IGF-I;143
8.3.5;STUDIES WITH GENETIC MUTANTS;147
8.3.6;DWARF RATS;148
8.3.7;CONCLUDING REMARKS;149
8.3.8;ACKNOWLEDGEMENTS;150
8.3.9;REFERENCES;150
8.4;Chapter 14. ACTION OF IGF-I ON MAMMARY FUNCTION;152
8.4.1;INTRODUCTION;152
8.4.2;ROLE OF INSULIN IN MAMMARY FUNCTION;152
8.4.3;IGF RECEPTORS;153
8.4.4;ROLE OF IGF-I IN MAMMARY FUNCTION IN VIVO;154
8.4.5;CONCLUDING REMARKS;158
8.4.6;ACKNOWLEDGEMENTS;158
8.4.7;REFERENCES;158
8.5;Chapter 15. CHANGES IN INSULIN AND SOMATOMEDIN RECEPTORS AND UPTAKEOF INSULIN, IGF-I AND IGF-II DURING MAMMARY GROWTH,LACTOGENESIS AND LACTATION;164
8.5.1;BACKGROUND;164
8.5.2;INSULIN;164
8.5.3;INSULIN-LIKE GROWTH FACTOR I;166
8.5.4;INSULIN-LIKE GROWTH FACTOR II;170
8.5.5;REFERENCES;172
8.6;PARTICIPANTS;278
9;Part 3. IMMUNOLOGICAL ENHANCEMENT;176
9.1;Chapter 16. ANTIGEN-ANTIBODY COMPLEXES THAT ENHANCE GROWTH;178
9.1.1;INTRODUCTION;178
9.1.2;MONOCLONAL ANTIBODIES;178
9.1.3;GH/MAb COMPLEXES AND GROWTH;179
9.1.4;GH/MAb COMPLEXES AND BODY COMPOSITION;181
9.1.5;GH/MAb COMPLEXES AND LACTOGENIC ACTIVITY;182
9.1.6;GH/MAb COMPLEXES AND RECEPTOR BINDING;182
9.1.7;COVALENT LINKING STUDIES;183
9.1.8;MECHANISM OF ENHANCEMENT;185
9.1.9;ENHANCEMENT OF GH ACTIVITY BY ACTIVE IMMUNIZATION;186
9.1.10;CONCLUSIONS;186
9.1.11;REFERENCES;186
10;Part 4. TRANSGENICS;190
10.1;Chapter 17. INSERTION OF GROWTH HORMONE GENES INTO PIG EMBRYOS;192
10.1.1;INTRODUCTION;192
10.1.2;INTEGRATION OF FUSION GENES;193
10.1.3;EXPRESSION OF INTEGRATED GENES;193
10.1.4;PERFORMANCE AND PHYSIOLOGICAL CHARACTERISTICS;195
10.1.5;TRANSMISSION OF TRANSGENES;197
10.1.6;CONCLUSIONS;197
10.1.7;REFERENCES;197
10.2;Chapter 18. INDUCED EXPRESSION OF A BOVINE GROWTH HORMONE CONSTRUCT INTRANSGENIC PIGS;200
10.2.1;INTRODUCTION;200
10.2.2;PRODUCTION OF TRANSGENIC PIGS;201
10.2.3;INTEGRATION OF TRANSGENE;201
10.2.4;EXPRESSION OF TRANSGENE;202
10.2.5;INDUCED EXPRESSION;202
10.2.6;COMMENT;205
10.2.7;REFERENCES;209
11;Part 5. ACCEPTABILITY OFBIOTECHNOLOGY;212
11.1;Chapter 19. CRITERIA FOR THE PUBLIC ACCEPTABILITY OF BIOTECHNOLOGICAL INNOVATIONS IN ANIMAL PRODUCTION;214
11.1.1;INTRODUCTION;214
11.1.2;CATEGORIES OF SOCIETY;214
11.1.3;PHYSIOLOGICAL CRITERIA;215
11.1.4;PROCEDURAL CRITERIA;216
11.1.5;RECOMMENDATIONS;220
11.1.6;CODA;220
11.1.7;REFERENCES;221
12;Part 6. POSTERS;224
12.1;Chapter 20. INDEX OF POSTERS;226
12.2;Chapter 21. STRUCTURE AND REGULATION OF THE RAT GROWTH HORMONE RECEPTOR;232
12.2.1;REFERENCE;232
12.3;Chapter 22. CLONING AND ANALYSIS OF EXPRESSION OF RAT GROWTH HORMONER ECEPTOR;233
12.4;Chapter 23. CONFORMATIONAL ANALYSIS OF BOVINE GROWTH HORMONE FRAGMENTS WHICH CORRESPOND TO HELICAL REGIONS OFTHE INTACT PROTEIN;233
12.4.1;REFERENCES;233
12.5;Chapter 24. BIOLOGICAL ACTIVITY OF AMINO-TERMINAL AMINO ACID VARIANTS OF BOVINE SOMATOTROPIN;234
12.5.1;REFERENCES;234
12.6;Chapter 25. PURIFICATION AND PROPERTIES OF TWO RECOMBINANT DNA-DERIVEDOVINE GROWTH HORMONE VARIANTS EXPRESSED IN ESCHERICHIA COLI;235
12.6.1;REFERENCES;235
12.7;Chapter 26. GH TREATMENT OF HYPOPHYSECTOMIZED RATS: HORMONE AND NUTRIENT INTERACTIONS ON TISSUE METABOLISM;236
12.8;Chapter 27. HUMAN GROWTH HORMONE TREATMENT ENHANCES DEPOSITION OFCOLLAGEN IN RAT SKELETAL MUSCLES;237
12.8.1;REFERENCES;237
12.9;Chapter 28. METABOLIC AND ENDOCRINE CHALLENGE OF SOMATOTROPIN TREATED PIGS;238
12.9.1;REFERENCES;238
12.10;Chapter 29. EFFECT OF SOMATOTROPIN ON NITROGEN AND ENERGY METABOLISM IN GROWING SWINE;239
12.10.1;REFERENCES;239
12.11;Chapter 30. ANTI-LIPOGENIC EFFECTS OF SOMATOTROPIN ON OVINE ADIPOSE TISSUE;240
12.11.1;REFERENCES;240
12.12;Chapter 31. INCREASES IN SHEEP ADIPOCYTE ß-RECEPTOR NUMBER ON EXPOSURETO GROWTH HORMONE IN VITRO;241
12.12.1;REFERENCES;241
12.13;Chapter 32. THE EFFECT OF GROWTH HORMONE ON HIND-LIMB MUSCLEMETABOLISM IN GROWING LAMBS;242
12.14;Chapter 33. THE EFFECT OF GROWTH HORMONE ON MUSCLE ENZYME ACTIVITYAND LACTATE DEHYDROGENASE ISOENZYME PATTERN;243
12.14.1;REFERENCES;243
12.15;Chapter 34. THE EFFECTS OF CLOSE-ARTERIAL INFUSION OF CIMATEROL INTO THE HIND-LIMB OF GROWING LAMBS;244
12.15.1;REFERENCE;244
12.16;Chapter 35. MANIPULATION OF GROWTH IN ENTIRE MALE SHEEP BY THE BETAADRENERGIC AGONIST CIMATEROL AT TWO LEVELS OF DIETARY PROTEIN;245
12.17;Chapter 36. GROWTH HORMONE RELEASE IN CALVES SELECTED FOR HIGH ANDLOW DAIRY MERIT;246
12.17.1;REFERENCES;246
12.18;Chapter 37. THE INFLUENCE OF BOVINE SOMATOTROPIN (BST) ON LEUKOCYTEINSULIN RECEPTORS IN LACTATING COWS AND BEEF STEERS;247
12.18.1;REFERENCES;247
12.19;Chapter 38. BLOOD CONSTITUENTS AND SUBCUTANEOUS ADIPOSE TISSUE METABOLISM OF DAIRY COWS AFTER ADMINISTRATION OF RECOMBINANT BOVINE SOMATOTROPIN (bST) IN A PROLONGEDRELEASE FORMULATION;248
12.20;Chapter 39. THE EFFECT OF RECOMBINANT BOVINE SOMATOTROPIN (bST) IN ASUSTAINED RELEASE VEHICLE ON THE PERFORMANCE OF DAIRY COWS;249
12.21;Chapter 40. CHANGES IN MAMMARY UPTAKE OF ESSENTIAL AMINO ACIDS INLACTATING JERSEY COWS IN RESPONSE TO EXOGENOUS BOVINEPITUITARY SOMATOTROPIN;250
12.21.1;REFERENCE;250
12.22;Chapter 41. BIOCHEMICAL RESPONSES TO THE USE OF RECOMBINANT BOVINE SOMATOTROPIN (SOMETRIBOVE) IN DAIRY CATTLE IN RELATIONTO PRODUCTION AND WELFARE;251
12.22.1;REFERENCE;251
12.23;Chapter 42. ROLE OF FEVER ON THE ENDOTOXIN-INDUCED SOMATOTROPIN RELEASE IN THE LACTATING GOAT;252
12.23.1;ACKNOWLEDGEMENTS;253
12.23.2;REFERENCES;253
12.24;Chapter 43. EFFECTS OF RECOMBINANT PORCINE GROWTH HORMONE IN GERMAN PIG BREEDS DURING GROWTH AND LACTATION;254
12.25;Chapter 44. SEMISYNTHESIS OF INSULINS WITH MODIFIED GROWTH PROMOTING PROPERTIES;255
12.25.1;REFERENCES;255
12.26;Chapter 45. IDENTIFICATION OF THE PORCINE INSULIN-LIKE GROWTH FACTOR(IGF)I GENE PROMOTER REGION;255
12.26.1;REFERENCES;256
12.27;Chapter 46. STUDIES ON THE SECRETION OF HUMAN PROINSULIN AND INSULIN-LIKE GROWTH FACTORS I AND II IN E.COLI;257
12.27.1;REFERENCES;257
12.28;Chapter 47. INSULIN-LIKE GROWTH FACTOR (IGF) I AND II mRNA LEVELS IN THETISSUES OF THE OVINE FETUS AND NEONATE;258
12.28.1;REFERENCES;258
12.29;Chapter 48. LEVELS OF INSULIN-LIKE GROWTH FACTOR I IN SHEEP TISSUES;259
12.29.1;REFERENCES;259
12.30;Chapter 49. MODULATION OF INSULIN-LIKE GROWTH FACTOR I AND II mRNA DURING LOCALIZED GROWTH OF RAT SKELETAL MUSCLE AND BROWN ADIPOSE TISSUE;260
12.30.1;REFERENCES;260
12.31;Chapter 50. IDENTIFICATION OF IGF-I mRNA IN RABBIT MAMMARY GLAND AND EVOLUTION DURING PREGNANCY AND LACTATION;261
12.31.1;REFERENCES;261
12.32;Chapter 51. TISSUE-SPECIFIC AND DEVELOPMENTAL EXPRESSION OF INSULIN-LIKE GROWTH FACTOR-I IN THE PREGNANT AND LACTATING PIG;262
12.32.1;REFERENCES;262
12.33;Chapter 52. IGF-BINDING PROTEINS FROM PIG PRE-IMPLANTATION BLASTOCYSTS;263
12.33.1;REFERENCES;263
12.34;Chapter 53. INSULIN-DEPENDENCE OF THE SMALL IGF-BINDING PROTEIN (IGF-SBP);264
12.35;Chapter 54. TRANSFER OF PLASMA IGF-I INTO LYMPH;265
12.35.1;REFERENCE;265
12.36;Chapter 55. GROWTH HORMONE (bST), INSULIN, INSULIN LIKE GROWTH FACTOR I(IGF-I) AND IGF-I BINDING PROTEINS DURING LACTATION INCATTLE;266
12.37;Chapter 56. THE EFFECT OF NUTRITIONAL STATUS AND GROWTH HORMONE (GH)TREATMENT ON THE IN VITRO MITOGENIC RESPONSES OF MAMMARY GLAND TISSUE IN LAMBS;267
12.38;Chapter 57. COMPARATIVE ASPECTS OF SELECTED HORMONES AND GROWTH FACTORS ON PROTEIN METABOLISM IN ADULT AND FETAL OVINE PRIMARY MUSCLE CULTURES;268
12.38.1;REFERENCE;268
12.39;Chapter 58. INDUCTION OF LACTOGENIC RECEPTORS IN HYPOPHYSECTOMIZED RATS TREATED WITH BOVINE GROWTH HORMONE-MONOCLONAL ANTIBODY COMPLEXES;269
12.39.1;REFERENCES;269
12.40;Chapter 59. POTENTIATION OF GROWTH HORMONE ACTIVITY USING A POLYCLONAL ANTIBODY OF RESTRICTED SPECIFICITY;270
12.41;Chapter 60. PROTEINS COVALENTLY LINKED TO HUMAN GROWTH HORMONE WILLENHANCE ITS ACTIVITY IN VIVO;271
12.41.1;REFERENCES;271
12.42;Chapter 61. THE EFFECT OF IMMUNONEUTRALIZATION OF CRF ON THE GROWTH OF LAMBS;272
12.42.1;REFERENCES;272
12.43;Chapter 62. EFFECTS OF PASSIVE IMMUNIZATION WITH AN INSULIN-LIKE GROWTH FACTOR-I (IGF-I) MONOCLONAL ANTIBODY (MAB) ON GROWTH AND PITUITARY GROWTH HORMONE (GH) CONTENT INTHE GUINEA PIG;273
12.44;Chapter 63. CONTROL OF GROWTH HORMONE SECRETION DURING GESTATION AND LACTATION IN GILTS ACTIVELY IMMUNIZED AGAINST GROWTH HORMONE-RELEASING FACTOR;274
12.44.1;REFERENCE;274
12.45;Chapter 64. IMMUNIZATION AGAINST GROWTH HORMONE-RELEASING FACTOR SUPPRESSES IGF-I AND ABOLISHES OPIOID AGONIST INDUCED RELEASE OF GROWTH HORMONE IN LACTATING CATTLE;275
12.45.1;REFERENCE;275
12.46;Chapter 65. GROWTH HORMONE EXPRESSION AND EFFECTS IN TRANSGENIC SHEEP;276
12.46.1;REFERENCES;276
13;INDEX;290

Leseproben

SPECIES SPECIFICITY AND STRUCTURE-FUNCTION RELATIONSHIPS OF GROWTH HORMONE

M. Wallis,     Biochemistry Laboratory, School of Biological Sciences, University of Sussex, Falmer, Brighton BN1 9QG, U.K.

Publisher Summary

This chapter describes the species specificity and structure–function relationships of growth hormone (GH). GH is a protein hormone derived from the anterior pituitary gland. It comprises a single polypeptide chain of about 190 amino acids, containing two intrachain disulfide bridges. The apparent rapid evolution of GH in the primates makes sequence studies on GH for primates other than man of particular interest. The sequence of GH from the rhesus monkey has been reported. This is very similar to that of human GH, differing at only four residues, suggesting that the rate or evolution of GH because the divergence of old-world monkeys and great apes has been slow. The implication is that GH underwent a period of remarkably rapid evolution early in primate evolution. An alternative explanation is that the primate and nonprimate GH genes are not strictly homologous, implying that a second gene is present in the human genome, homologous with nonprimate GHs and a second gene is present in the nonprimate mammalian genome, homologous with human GH. The situation is complicated by the occurrence of a cluster of GH-like genes in man.

INTRODUCTION

Growth hormone (GH) is a protein hormone derived from the anterior pituitary gland. It comprises a single polypeptide chain of about 190 amino acids, containing two intrachain disulphide bridges. In some species there is a tendency for the polypeptide chain to associate to form dimers or larger aggregates, but it is not clear whether this has any biological significance. GHs are found in all vertebrate groups except possibly the primitive, jawless fishes (Agnatha). There are considerable differences between GHs obtained from different groups, however, in both structure and biological properties.

In this paper I shall survey current knowledge about the species specificity of GHs. concentrating mainly on the differences between the primary structures for which information is available. Some aspects of the relationship between structure and function in GH will also be considered.

MICROHETEROGENEITY OF GROWTH HORMONE

Although for any one species it is normal to refer to GH as a single component, the hormone in many species is known to exist in a number of different forms. As a consequence, GH isolated from anterior pituitaries usually shows microheterogeneity. Such heterogeneity may arise from a number of causes, including the occurrence of more than one gene for the hormone, variant forms of mRNA due to different processing pathways for the mRNA precursors, allelic variation in the population of animals from which the hormone is derived, variable glycosylation (although in most species GH is not glycosylated), limited enzymic cleavage, N-terminal heterogeneity and deamidation. Heterogeneity has been most extensively studied in the case of human GH (20), but occurs in GHs from most other species also. Its physiological significance, if any, is not fully understood, but its possible importance should be borne in mind when species differences and structure-function relationships are discussed.

SPECIES SPECIFICITY OF GROWTH HORMONES: VARIATIONS IN AMINO ACID SEQUENCE

The first GH for which the amino acid sequence was reported was the human hormone (25). Subsequent work on GHs from a number of species produced the sequences of ovine, bovine, horse and pig GHs (summarized in Ref. 40) and revision of the human GH sequence. In 1977 application of the techniques of recombinant DNA allowed the sequence of rat GH to be deduced from the corresponding cDNA/mRNA nucleotide sequence (32). Since then application of both recombinant DNA techniques and conventional protein sequencing has increased the number of complete GH sequences available to at least 20 including 2 primates. 9 non-primate mammals, 2 birds, 1 amphibian and 7 teleost fish. Some of these sequences are summarized in Fig. 1; some are based on protein sequencing, some on cDNA/genomic DNA sequencing and some on both.

Fig. 1 The amino acid sequences of some tetrapod GHs (see opposite)

The availability of sequences for GHs from such a considerable number of species enables detailed comparisons to be made and assessment of possible pathways of molecular evolution in this protein-hormone family. These have been discussed previously (26, 27 41). The additional sequences that have been described in the past few years provide confirmation of the main features recognized previously, particularly with respect to apparently variable rates of evolution.

When the amino acid sequences of non-primate mammalian GHs are compared it is clear that they are very similar. However, when any of these sequences (or a consensus sequence derived from them) is compared with the sequence of human GH the difference is marked (41). The various orders of placental mammals are thought to have diverged at about the same time, 70 million years ago. The divergence time for rat and human is therefore about the same as that for rat and pig; however, rat GH differs from human GH at ~ 35% of all residues but from pig GH at ~ 5% of all residues. Such observations suggest that the rate of evolution of GHs in the primates has been much greater than that in non-primate mammals. A variable rate of evolution within a protein family is relatively unusual – normally it is found that the rate of evolution for any individual protein is remarkably constant (though rates vary from one protein to another; eg Ref. 16). The rate of evolution can be quantified by determining a most probable sequence for the GH of the ancestor of the placental mammals (from sequence data available for exisiting mammals) (41). This is very similar to the sequences of pig. fin whale and horse GHs (Fig. 1). The number of amino acid differences observed between the existing GH sequences and this ancestral sequence can then be used to determine the rates of evolution for GH in each of the groups concerned (Table 1).

Table 1

Rates of evolution for growth hormones

*Accepted point mutations/100 residues/108 yr

**’Placental ancestor’ represents the hypothetical GH sequence of the common ancestor of the placental mammals.

A hypothetical (best fit sequence for the GH of the common ancestor of the placental mammals (Anc. p.m.) was derived from available GH sequences, using methods described previously (41). This is shown, using one-letter code. Sequences of various tetrapod GHs are compared with this. A solid line indicates sequence identity; differences are shown using one-letter code; – indicates a gap. Note that the sequences of pig, horse and whale GHs are very similar to the ancestral sequence but those of man, chicken and bullfrog differ from it substantially. Original data for the sequences shown may be found in Refs. 32 (rat), 34 (chicken). 33 (pig). 38 (whale). 29 (bullfrog) or references cited in Ref. 41 (horse, man. ox).

The apparent rapid evolution of GH in the primates makes sequence studies on GH for primates other than man of particular interest. The sequence of GH from the rhesus monkey has been reported (23). This is very similar to that of human GH, differing at only 4 residues, suggesting that the rate of evolution of GH since the divergence of old-world monkeys and great apes (approximately 20 million years ago) has been slow. The implication is that GH underwent a period of remarkably rapid evolution early in primate evolution. An alternative explanation is that the primate and non-primate GH genes are not strictly homologous, implying that a second gene (or family of genes) is present in the human genome, homologous with non-primate GHs (but not expressed as a major form in the pituitary) and a second gene is present in the non-primate mammalian genome, homologous with human GH (but again not expressed in the pituitary). The situation is complicated by the occurrence of a cluster of GH-like genes in man (eg Ref. 12). More information is needed, especially about GH (and GH genes) in other primates. However, it is clear that the nature of GH in primates and non-primates is remarkably different and this must be taken into account when considering the biological actions of the hormone in different species.

The rate of evolution of GHs also appears to have increased, though to a less marked extent, during the evolution of the ruminants (Table 1). The sequences of sheep, ox and goat GHs have all been determined; they show marked similarities. Sequences of any of these ruminant GHs differ from the sequences of rat or pig GHs at about 11% of all residues, whereas the rat, horse, fin whale and pig hormones differ at only 1–5% of all residues.

Most previous discussion of GH evolution has concentrated on mammalian GHs. Sequences of several non-mammalian GHs are now available. In general they are fairly similar to the sequences of the non-primate mammalian GHs. Sequences of GHs from bird (chicken and duck) (5, 34) are more similar to the non-primate GHs than the latter are to human GH, confirming the very rapid evolution...